Journal of Computer-Aided Molecular Design

, Volume 19, Issue 7, pp 465–481

A recursive-partitioning model for blood–brain barrier permeation

Article

DOI: 10.1007/s10822-005-9001-7

Cite this article as:
Mente*, S. & Lombardo, F. J Comput Aided Mol Des (2005) 19: 465. doi:10.1007/s10822-005-9001-7

Summary

A series of bagged recursive partitioning models for log(BB) is presented. Using a LGO-CV, three sets of physical property descriptors are evaluated and found to have Q2 values of 0.51 (CPSA), 0.53 (Ro5x) and 0.53 (MOE). Extrapolating these models to Pfizer chemical space is difficult due to P-glycoprotein (P-gp) mediated efflux. Low correlation coefficients for this test set are improved (R2=0.39) when compounds known to be P-gp substrates or statistical extrapolations are removed. The use of simple linear models for specific chemical series is also found to improve the correlation over a limited chemical space.

Keywords

ADME blood–brain barrier CNS in silico QSAR 

Supplementary material

10822_2005_9001_MOESM1_ESM.pdf (218 kb)
Supplementary material

Copyright information

© Springer science + business media 2005

Authors and Affiliations

  1. 1.Pfizer Global Research and DevelopmentGrotonUSA

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